Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.23.5 (cathepsin D)
 4,130 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Vitamin E is a generic term used to indicate all tocopherol (TOC) and tocotrienol (TT) derivates. In the last few years, several papers have shown that a TT-rich fraction (TTRF) extracted from palm oil inhibits proliferation and induces apoptosis in a large number of cancer cells. However, the molecular mechanism(s) involved in TT action is still unclear. In the present study, we proposed for the first time a novel mechanism for TT activity that involves estrogen receptor (ER) signaling. In silico simulations and in vitro binding analyses indicated a high affinity of TTs for ERbeta but not for ERalpha. In addition, in ERbeta-containing MDA-MB-231 breast cancer cells, we demonstrated that TTs increase the ERbeta translocation into the nucleus, which in turn activates estrogen-responsive genes (MIC-1, EGR-1 and cathepsin D), as demonstrated by cell preincubation with the ER inhibitor ICI-182,780. Finally, we observed that TT treatment is associated with alteration of cell morphology, DNA fragmentation, and caspase-3 activation. Altogether, these experiments elucidated the molecular mechanism underling gamma- and delta-TT effects.
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PMID:A novel mechanism of natural vitamin E tocotrienol activity: involvement of ERbeta signal transduction. 1949 Dec 96

Human telomerase reverse transcriptase (hTERT) contributes to tumor progression as well as maintaining telomere length, however, the mechanism by which hTERT promotes invasiveness is not yet completely understood. This study aims to unravel the precise mechanism through which hTERT promotes cancer invasion. We established an hTERT-overexpressed immortalized cell line (IHOK/hTERT). In orthotopic xenograft models, IHOK/hTERT harbors higher tumorigenicity than IHOK/Control. IHOK/hTERT showed much higher migration and invasion activities compared to IHOK/Control. IHOK/hTERT co-cultured with fibroblasts displayed increased invasion compared to IHOK/hTERT without fibroblasts. We screened for genes that play an important role in intermodulation between cancer cells and fibroblasts using a microarray and identified fibroblast activation protein (FAP). hTERT knockdown showed decreased expression of FAP and early growth response (EGR)-1, one of the transcriptional regulators of FAP in IHOK/hTERT and oral cancer cell line YD10B. Furthermore, EGR-1 knockdown in IHOK/hTERT and YD10B showed reduced invasion and reduced cathepsin D expression compared to Control-siRNA cells. Taken together, this study provides evidence that hTERT overexpression is responsible for the upregulation of the cysteine protease cathepsin D by regulating EGR-1 to activate invasiveness in cancer progression.
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PMID:Human telomerase reverse transcriptase (hTERT) promotes cancer invasion by modulating cathepsin D via early growth response (EGR)-1. 2651 55